Induction of endoplasmic reticulum calcium pump expression during early leukemic B cell differentiation
Identifieur interne : 004A45 ( Ncbi/Checkpoint ); précédent : 004A44; suivant : 004A46Induction of endoplasmic reticulum calcium pump expression during early leukemic B cell differentiation
Auteurs : Lamia Aït Ghezali [France] ; Atousa Arbabian [France] ; Hervé Roudot [France] ; Jean-Philippe Brouland [France] ; Fanny Baran-Marszak [France] ; Evelyn Salvaris ; Andrew Boyd [Australie] ; Hans G. Drexler [Allemagne] ; Agnes Enyedi [Hongrie] ; Remi Letestu [France] ; Nadine Varin-Blank [France] ; Bela Papp [France]Source :
- Journal of Experimental & Clinical Cancer Research : CR [ 0392-9078 ] ; 2017.
Abstract
Endoplasmic reticulum (ER) calcium storage and release play important roles in B lymphocyte maturation, survival, antigen-dependent cell activation and immunoglobulin synthesis. Calcium is accumulated in the endoplasmic reticulum (ER) by Sarco/Endoplasmic Reticulum Calcium ATPases (SERCA enzymes). Because lymphocyte function is critically dependent on SERCA activity, it is important to understand qualitative and quantitative changes of SERCA protein expression that occur during B lymphoid differentiation and leukemogenesis.
In this work we investigated the modulation of SERCA expression during the pharmacologically induced differentiation of leukemic precursor B lymphoblast cell lines that carry the E2A-PBX1 fusion oncoprotein. Changes of SERCA levels during differentiation were determined and compared to those of established early B lymphoid differentiation markers. SERCA expression of the cells was compared to that of mature B cell lines as well, and the effect of the direct inhibition of SERCA-dependent calcium transport on the differentiation process was investigated.
We show that E2A-PBX1+ leukemia cells simultaneously express SERCA2 and SERCA3-type calcium pumps; however, their SERCA3 expression is markedly inferior to that of mature B cells. Activation of protein kinase C enzymes by phorbol ester leads to phenotypic differentiation of the cells, and this is accompanied by the induction of SERCA3 expression. Direct pharmacological inhibition of SERCA-dependent calcium transport during phorbol ester treatment interferes with the differentiation process.
These data show that the calcium pump composition of the ER is concurrent with increased SERCA3 expression during the differentiation of precursor B acute lymphoblastic leukemia cells, that a cross-talk exists between SERCA function and the control of differentiation, and that SERCA3 may constitute an interesting new marker for the study of early B cell phenotype.
The online version of this article (doi:10.1186/s13046-017-0556-7) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1186/s13046-017-0556-7
PubMed: 28651627
PubMed Central: 5485704
Affiliations:
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<affiliation wicri:level="1"><nlm:aff id="Aff1">Institut National de la Santé et de la Recherche Médicale, U978 Bobigny, France</nlm:aff>
<country xml:lang="fr">France</country>
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<wicri:noRegion>U978 Bobigny</wicri:noRegion>
<wicri:noRegion>U978 Bobigny</wicri:noRegion>
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<institution></institution>
<institution>Université Paris-13, PRES Sorbonne Paris-Cité,</institution>
</institution-wrap>
74, rue Marcel Cachin 93017, Bobigny, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>74, rue Marcel Cachin 93017, Bobigny</wicri:regionArea>
<wicri:noRegion>93017, Bobigny</wicri:noRegion>
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<institution-id institution-id-type="GRID">grid.413780.9</institution-id>
<institution>Service d’Hématologie Biologique,</institution>
<institution>Hôpitaux Universitaires Paris Seine-Saint-Denis, AP-HP, Hôpital Avicenne,</institution>
</institution-wrap>
Bobigny, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Bobigny</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Salvaris, Evelyn" sort="Salvaris, Evelyn" uniqKey="Salvaris E" first="Evelyn" last="Salvaris">Evelyn Salvaris</name>
<affiliation><nlm:aff id="Aff6"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 8606 2560</institution-id>
<institution-id institution-id-type="GRID">grid.413105.2</institution-id>
<institution>Immunology Research Centre,</institution>
<institution>St Vincent’s Hospital,</institution>
</institution-wrap>
Melbourne, VIC Australia</nlm:aff>
<wicri:noCountry code="subfield">VIC Australia</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Boyd, Andrew" sort="Boyd, Andrew" uniqKey="Boyd A" first="Andrew" last="Boyd">Andrew Boyd</name>
<affiliation wicri:level="1"><nlm:aff id="Aff7"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9320 7537</institution-id>
<institution-id institution-id-type="GRID">grid.1003.2</institution-id>
<institution>Department of Medicine,</institution>
<institution>University of Queensland,</institution>
</institution-wrap>
Queensland, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Queensland</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Drexler, Hans G" sort="Drexler, Hans G" uniqKey="Drexler H" first="Hans G." last="Drexler">Hans G. Drexler</name>
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<institution-id institution-id-type="GRID">grid.420081.f</institution-id>
<institution></institution>
<institution>Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH,</institution>
</institution-wrap>
Brauschweig, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Brauschweig</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Enyedi, Agnes" sort="Enyedi, Agnes" uniqKey="Enyedi A" first="Agnes" last="Enyedi">Agnes Enyedi</name>
<affiliation wicri:level="1"><nlm:aff id="Aff9"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0942 9821</institution-id>
<institution-id institution-id-type="GRID">grid.11804.3c</institution-id>
<institution>Second Institute of Pathology,</institution>
<institution>Semmelweis University Medical School,</institution>
</institution-wrap>
Budapest, Hungary</nlm:aff>
<country xml:lang="fr">Hongrie</country>
<wicri:regionArea>Budapest</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Letestu, Remi" sort="Letestu, Remi" uniqKey="Letestu R" first="Remi" last="Letestu">Remi Letestu</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1">Institut National de la Santé et de la Recherche Médicale, U978 Bobigny, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, U978 Bobigny</wicri:regionArea>
<wicri:noRegion>U978 Bobigny</wicri:noRegion>
<wicri:noRegion>U978 Bobigny</wicri:noRegion>
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<institution-id institution-id-type="GRID">grid.11318.3a</institution-id>
<institution></institution>
<institution>Université Paris-13, PRES Sorbonne Paris-Cité,</institution>
</institution-wrap>
74, rue Marcel Cachin 93017, Bobigny, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>74, rue Marcel Cachin 93017, Bobigny</wicri:regionArea>
<wicri:noRegion>93017, Bobigny</wicri:noRegion>
<wicri:noRegion>93017, Bobigny</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 8715 2621</institution-id>
<institution-id institution-id-type="GRID">grid.413780.9</institution-id>
<institution>Service d’Hématologie Biologique,</institution>
<institution>Hôpitaux Universitaires Paris Seine-Saint-Denis, AP-HP, Hôpital Avicenne,</institution>
</institution-wrap>
Bobigny, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Bobigny</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Varin Blank, Nadine" sort="Varin Blank, Nadine" uniqKey="Varin Blank N" first="Nadine" last="Varin-Blank">Nadine Varin-Blank</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1">Institut National de la Santé et de la Recherche Médicale, U978 Bobigny, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, U978 Bobigny</wicri:regionArea>
<wicri:noRegion>U978 Bobigny</wicri:noRegion>
<wicri:noRegion>U978 Bobigny</wicri:noRegion>
</affiliation>
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<institution-id institution-id-type="GRID">grid.11318.3a</institution-id>
<institution></institution>
<institution>Université Paris-13, PRES Sorbonne Paris-Cité,</institution>
</institution-wrap>
74, rue Marcel Cachin 93017, Bobigny, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>74, rue Marcel Cachin 93017, Bobigny</wicri:regionArea>
<wicri:noRegion>93017, Bobigny</wicri:noRegion>
<wicri:noRegion>93017, Bobigny</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Papp, Bela" sort="Papp, Bela" uniqKey="Papp B" first="Bela" last="Papp">Bela Papp</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1">Institut National de la Santé et de la Recherche Médicale, U978 Bobigny, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, U978 Bobigny</wicri:regionArea>
<wicri:noRegion>U978 Bobigny</wicri:noRegion>
<wicri:noRegion>U978 Bobigny</wicri:noRegion>
</affiliation>
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<institution-id institution-id-type="GRID">grid.11318.3a</institution-id>
<institution></institution>
<institution>Université Paris-13, PRES Sorbonne Paris-Cité,</institution>
</institution-wrap>
74, rue Marcel Cachin 93017, Bobigny, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>74, rue Marcel Cachin 93017, Bobigny</wicri:regionArea>
<wicri:noRegion>93017, Bobigny</wicri:noRegion>
<wicri:noRegion>93017, Bobigny</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff10"><institution-wrap><institution-id institution-id-type="ISNI">0000000121496883</institution-id>
<institution-id institution-id-type="GRID">grid.11318.3a</institution-id>
<institution></institution>
<institution>U978 Inserm, UFR SMBH, Université Paris-13,</institution>
</institution-wrap>
74, rue Marcel Cachin, 93017 Bobigny, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>74, rue Marcel Cachin, 93017 Bobigny</wicri:regionArea>
<wicri:noRegion>93017 Bobigny</wicri:noRegion>
<wicri:noRegion>93017 Bobigny</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">Journal of Experimental & Clinical Cancer Research : CR</title>
<idno type="ISSN">0392-9078</idno>
<idno type="eISSN">1756-9966</idno>
<imprint><date when="2017">2017</date>
</imprint>
</series>
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<front><div type="abstract" xml:lang="en"><sec><title>Background</title>
<p id="Par1">Endoplasmic reticulum (ER) calcium storage and release play important roles in B lymphocyte maturation, survival, antigen-dependent cell activation and immunoglobulin synthesis. Calcium is accumulated in the endoplasmic reticulum (ER) by Sarco/Endoplasmic Reticulum Calcium ATPases (SERCA enzymes). Because lymphocyte function is critically dependent on SERCA activity, it is important to understand qualitative and quantitative changes of SERCA protein expression that occur during B lymphoid differentiation and leukemogenesis.</p>
</sec>
<sec><title>Methods</title>
<p id="Par2">In this work we investigated the modulation of SERCA expression during the pharmacologically induced differentiation of leukemic precursor B lymphoblast cell lines that carry the E2A-PBX1 fusion oncoprotein. Changes of SERCA levels during differentiation were determined and compared to those of established early B lymphoid differentiation markers. SERCA expression of the cells was compared to that of mature B cell lines as well, and the effect of the direct inhibition of SERCA-dependent calcium transport on the differentiation process was investigated.</p>
</sec>
<sec><title>Results</title>
<p id="Par3">We show that E2A-PBX1<sup>+</sup>
leukemia cells simultaneously express SERCA2 and SERCA3-type calcium pumps; however, their SERCA3 expression is markedly inferior to that of mature B cells. Activation of protein kinase C enzymes by phorbol ester leads to phenotypic differentiation of the cells, and this is accompanied by the induction of SERCA3 expression. Direct pharmacological inhibition of SERCA-dependent calcium transport during phorbol ester treatment interferes with the differentiation process.</p>
</sec>
<sec><title>Conclusion</title>
<p id="Par4">These data show that the calcium pump composition of the ER is concurrent with increased SERCA3 expression during the differentiation of precursor B acute lymphoblastic leukemia cells, that a cross-talk exists between SERCA function and the control of differentiation, and that SERCA3 may constitute an interesting new marker for the study of early B cell phenotype.</p>
</sec>
<sec><title>Electronic supplementary material</title>
<p>The online version of this article (doi:10.1186/s13046-017-0556-7) contains supplementary material, which is available to authorized users.</p>
</sec>
</div>
</front>
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